In silico simulations of diffusion tensors and tortuosity in cells grown on 3D-printed scaffolds for tissue engineering

Tissue engineering is set to revolutionise regenerative medicine, drug discovery, and cancer biology. For this to succeed, improved 3D imaging methods that penetrate non-invasively into the developing tissue is fundamental to guide the design of new and improved 3D supports. In particular, it is very important to characterise the time- and space-heterogeneous pore network that continuously changes as the tissue grows, since delivery of nutrients and removal of waste is key to avoid the development of necrotic tissues. In this paper, we combine high-resolution microfocus Computed Tomography (μCT) imaging and in silico simulations to calculate the diffusion tensor of molecules diffusing in the actual pore structure of a tissue grown on 3D-printed plastic scaffolds. We use such tensors to derive information about the changing pore network and derive tortuosity, a key parameter to understand how pore interconnection changes with cell proliferation. Such information can be used to improve the design of 3D-printed supports as well as to validate and improve cell culture protocols.